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Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state.

Abstract：

:Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Morito D,Nishikawa K,Hoseki J,Kitamura A,Kotani Y,Kiso K,Kinjo M,Fujiyoshi Y,Nagata K

doi

10.1038/srep04442

subject

Has Abstract

pub_date

2014-03-24 00:00:00

pages

4442

issn

2045-2322

pii

srep04442

journal_volume

4

pub_type

杂志文章

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